Combination product for the treatment of cancer

Abstract

Methods of administering a therapeutically effective amount of Debio 1143 and a therapeutically effective amount of an anti-PD-L1 antibody or antigen-binding fragment thereof, for the treatment of cancer, are provided.

1 . A combination product comprising:
 (i) Debio 1143; and   (ii) an anti-PD-L1 antibody or antigen-binding fragment thereof.   
     
     
         2 . The combination product according to  claim 1 , wherein the combination product is a pharmaceutical combination product and further comprises a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant. 
     
     
         3 . A pharmaceutical composition comprising:
 (i) Debio 1143;   (ii) an anti-PD-L1 antibody or antigen-binding fragment thereof; and   (iii) a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant.   
     
     
         4 . The combination product according to  claim 1 , wherein the antibody or antigen-binding fragment thereof mediates antibody-dependent cellular cytotoxicity. 
     
     
         5 . The combination product according to  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein said VL comprises VL-CDR1, VL-CDR2 and VL-CDR3 polypeptides and VH comprises VH-CDR1, VH-CDR2 and VH-CDR3 polypeptides which are selected from the group consisting of: 
       
         
           
                 
                 
                 
               
                     
                   (a) 
                   VL-CDR1 is TGTSSDVGGYNYVS, 
                 
                     
                     
                 
                     
                     
                   VL-CDR2 is DVSNRPS, 
                 
                     
                     
                 
                     
                     
                   VL-CDR3 is SSYTSSSTRV, 
                 
                     
                     
                 
                     
                     
                   VH-CDR1 is SYIMM, 
                 
                     
                     
                 
                     
                     
                   VH-CDR2 is SIYPSGGITFYADTVKG, 
                 
                     
                     
                   and 
                 
                     
                     
                 
                     
                     
                   VH-CDR3 is IKLGTVTTVDY; 
                 
                     
                     
                 
                     
                   (b) 
                   VL-CDR1 is RASQDVSTAVA, 
                 
                     
                     
                 
                     
                     
                   VL-CDR2 is SASFLYS, 
                 
                     
                     
                 
                     
                     
                   VL-CDR3 is QQYLYHPAT, 
                 
                     
                     
                 
                     
                     
                   VH-CDR1 is GFTFSDSWIH, 
                 
                     
                     
                 
                     
                     
                   VH-CDR2 is AWISPYGGSTYYADSVKG, 
                 
                     
                     
                   and 
                 
                     
                     
                 
                     
                     
                   VH-CDR3 is RHWPGGFDY; 
                 
                     
                     
                   and 
                 
                     
                     
                 
                     
                   (c) 
                   VL-CDR1 is RASQRVSSSYLA, 
                 
                     
                     
                 
                     
                     
                   VL-CDR2 is DASSRAT, 
                 
                     
                     
                 
                     
                     
                   VL-CDR3 is QQYGSLPWT, 
                 
                     
                     
                 
                     
                     
                   VH-CDR1 is RYWMS, 
                 
                     
                     
                 
                     
                     
                   VH-CDR2 is NIKQDGSEKYYVDSVKG, 
                 
                     
                     
                   and 
                 
                     
                     
                   VH-CDR3 is EGGWFGELAFDY; 
                 
                     
                     
                 
                     
                     
                   preferably,  
                 
                     
                     
                   VL-CDR1 is TGTSSDVGGYNYVS, 
                 
                     
                     
                 
                     
                     
                   VL-CDR2 is DVSNRPS, 
                 
                     
                     
                 
                     
                     
                   VL-CDR3 is SSYTSSSTRV, 
                 
                     
                     
                 
                     
                     
                   VH-CDR1 is SYIMM, 
                 
                     
                     
                 
                     
                     
                   VH-CDR2 is SIYPSGGITFYADTVKG, 
                 
                     
                     
                   and 
                 
                     
                     
                 
                     
                     
                   VH-CDR3 is IKLGTVTTVDY. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . The combination product according to  claim 1 , wherein the antibody is avelumab. 
     
     
         7 . The combination product according to  claim 1 , wherein the anti-PD-L1 antibody and the Debio 1143 are provided in a single or separate unit dosage forms. 
     
     
         8 . (canceled) 
     
     
         9 . A method of treating cancer, comprising administering to a patient a combination product according to  claim 1 ; wherein, the cancer is selected from the group consisting of Lung Cancer, Head and Neck cancer, bladder cancer, kidney cancer, skin melanoma, colorectal cancer, ovarian cancer, breast cancer, non-Hodgkin lymphoma, and Hodgkin lymphomas. 
     
     
         10 . The method according to  claim 9 , wherein the cancer is Non-Small Cell Lung Cancer. 
     
     
         11 . The method according to  claim 9 , wherein the method comprises administering about 75 to about 250 mg Debio 1143 and about 10 mg/kg of the antibody or antigen-binding fragment thereof. 
     
     
         12 . The method according to  claim 9 , wherein the method of treatment comprises a 28-day cycle comprising
 (a) administering the Debio 1143 for a first 10 consecutive day period;   (b) administering no Debio 1143 for a first 4 consecutive day period;   (c) administering the Debio 1143 for a second 10 consecutive day period;   (d) administering no Debio 1143 for a second 4 consecutive day period;   (e) administering the avelumab on day 1 of the 28-day cycle; and   (f) administering the avelumab on day 15 of the 28-day cycle.   
     
     
         13 . The method according to  claim 9 , wherein the patient underwent at least one round of prior cancer therapy. 
     
     
         14 . The method according to  claim 9 , wherein the patient has previously received platinum-based therapy. 
     
     
         15 . A kit comprising an anti-PD-L1 antibody and Debio 1143, and a package insert comprising instructions for using the anti-PD-L1 antibody and Debio 1143 to treat or delay progression of a cancer in a patient. 
     
     
         16 . A method of treating cancer, comprising administering to a patient an anti-PD-L1 antibody in combination with Debio 1143. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 16 , wherein the anti-PD-L1 antibody and the Debio 1143 are administered sequentially. 
     
     
         19 . The method of  claim 16 , wherein the anti-PD-L1 antibody and the Debio 1143 are administered concurrently. 
     
     
         20 . The method of  claim 16 , wherein the antibody is avelumab. 
     
     
         21 . The method of  claim 18 , wherein the antibody is avelumab. 
     
     
         22 . The method according to  claim 10 , wherein the cancer is stage IIIB or stage IV Non-Small Cell Lung Cancer.